CYTOKINE NETWORKING BY ALVEOLAR MACROPHAGE IN ATOPIC PATIENTS WITH MILD ASTHMA.

In a previous study we demonstrated that alveolar macrophage obtained from BAL of asthmatic patients showed an "activated” state. Indeed, these cells reveaied an increased expression of the cell surface markers HLA-DR, CD23, CD44 and an enhanced secretion of LPS- Induced cytokines such as IL-1B (p = 0.05), IL-8 (p = 0.05), and TNFa (p = 0.03) in comparison with alveolar macrophage from normal subjects. In this study, we evaluated the time-course of the interleukin secretion IL-1B, IL-6, IL-8, TNFa in LPS-stimulated alveolar macrophage cultures obtained from BAL celLs in 8 asthmatic patients (mean ± SD age 29.4 ±8.1 yrs). The different cytokines concentration In the macrophage conditioned medium was assessed by ELISA; only for IL-8 we also evaluated the amount of the specific mRNA We demonstrated that the IL-1B and TFNa secretion was evident 4 hrs after LPS stimulation (respectivly IL-1B = 35 ng/ml and TNFa = 65 ng/ml), while the IL-6 secretion began only 8 hrs following LPS cell activation (IL-6 = 6 ng/ml). The IL-8 secretion presented a biphasic secretory pattern: a slight Increase during the first 12 hrs after LPS-stimulation (0 -12 ng/ml until 12 hrs) and a strong increase from 12»h until 24«h hour(12 - 36ng/ml). Furthermore, by using monoclonal antibodies anti TNFa and IL-1B we demonstrated that the IL-8 production depended on the presence of TNFa and IL-1B in the culture medium. Our results suggest that the cytokines production by alveolar macrophage presents a well-defined time-course In which the secretion of some cytokines, such as TNFa and IL-1B, shows a stimulatory effect on the secretion of the others (l.c. IL-8).